Functioning of oxytocin receptor in the central nervous system and smooth muscles

Moroz, O., Basovska, O., & Zholos, A. (2024). Functioning of oxytocin receptor in the central nervous system and smooth muscles. Fiziolohichnyĭ zhurnal, 70(1), 67–78. https://doi.org/10.15407/fz70.01.067

Investigation of the mechanism of neuronal communication underlies the fundamental discoveries that promote health. The studies of oxytocin signaling in neurons from or within different brain areas are directed to explore the role of this neurohormonal modulator in the regulation of synaptic transmission and plasticity, neuronal excitability that contributes to the reproduction, social behavior and learning capacity, anxiety, inflammation and differentiation in the brain. Oxytocin is synthesized in supraoptic and paraventricular nuclei of the hypothalamus and when secreted into the bloodstream from the posterior pituitary, it produces a significant effect on uterine contraction and lactation. At the same time this nonapeptide being released within the limbic system and brain cortex modulates neuronal activity by affecting ion channels on their membranes. The oxytocin receptor is primarily coupled to Gq/11 proteins causing phospholipase C activation, Ca2+ release and store-operated Ca2+ entry. These pathways are central for the regulation of the activity of different types of TRP channels, especially of the canonical subfamily (TRPC). Here we highlight the link between oxytocin signaling, which is particularly well investigated in the myometrium, and receptor-operated TRPC4 and multimodal TRPV4 ion channels that participate in oxytocin-dependent regulation of the uterine smooth muscle contractility under various conditions. Importantly, similarly to oxytocin, these channels have been implicated in neuropathic pain behavior, anxiety, fear and depression. Since similar signal transduction pathways are likely to be functional in neuronal cells, we propose that future studies of oxytocin effects in the CNS should also consider the role of these Ca2+-permeable channels.